Population Council researchers began working to develop an effective vaginal microbicide in the late 1980s.

They screened a broad range of chemical compounds for their ability to inhibit infection by HIV in laboratory tests (in vitro). Researchers identified a class of compounds called sulfated polysaccharides as promising candidate microbicides. Further research led to development of a small-animal system that would mimic the physiological events of human sexual transmission of HIV, which led to the identification of carrageenan as being significantly more effective in blocking infection in mice.

Carraguard (formerly known as PC-515) is the Population Council's first-generation candidate microbicide, a gel whose active ingredient is made from carrageenan, a substance derived from seaweed. Carrageenan is inexpensive and stable and has been used extensively in the food, pharmaceutical, and cosmetics industries as a gelling, stabilizing, dispersing, and thickening agent.

Carrageenan compounds are on the US Food and Drug Administration's list of GRAS (generally recognized as safe) products for consumption and topical application. Extensive studies to evaluate the breakdown, absorption, and safety of carrageenan were conducted in order to obtain the GRAS classification. The Population Council has conducted further nonclinical testing, which is required prior to clinical testing and is necessary in obtaining regulatory registration should the Phase 3 clinical trial show Carraguard to be efficacious. Nonclinical testing includes the evaluation of the pharmacological, quality, and toxicological effects of Carraguard.

Pharmacological testing has evaluated the effects of Carraguard on a range of sexually transmitted pathogens. Laboratory tests have shown that Carraguard blocks infection by HIV in vitro; and herpes simplex virus type 2 (HSV-2), human papillomavirus (HPV), and the gonorrhea-causing bacteria Neisseria both in vitro and in small-animal systems (in vivo).

Quality testing includes chemical identity to ensure chemical consistency between different lots of raw materials and different batches of Carraguard; impurity and microbiological analysis verifies the absence of any form of contamination; preservative effectiveness testing establishes that the type and concentration of the preservative is sufficient to retard against external contamination; degradation studies have shown that Carraguard is not degraded during the manufacturing process nor by the vaginal environment; and stability testing thus far has indicated that Carraguard is stable for two years.

Toxicological testing has established that Carraguard is compatible with the latex used to make condoms and diaphragms; is not carcinogenetic; is not toxic to vaginal cells in vitro and vaginal epithelia cells in rabbits; and does not enhance or inhibit the growth of normal vaginal flora. Reproductive toxicology studies conducted in mice and rabbits have demonstrated that Carraguard has no embryo/fetal or maternal toxicity through prenatal development.

Carraguard® is the Population Council's US trademark for pharmaceutical preparations, namely microbicides, for use in preventing infection.

Contact: microbicide@popcouncil.org